Pharmacology and Neuroscience

Dr. Paul R. Casner

Professor of Internal Medicine Ph.D., 1975, New York Medical CollegeM.D., 1980, New York Medical College

Diabetes, hypertension and drug metabolism:

Clinical Pharmacology

Our research is focused on clinical pharmacology and has involved studies involving
diabetes, hypertension and drug metabolism. In the field of diabetes our initial pharmacology
studies demonstrated that combination therapy of oral sulfonylureas with insulin was
beneficial in selected patients with type 2 diabetes. Patients with high C-peptide
levels were often able to reduce insulin requirements by 50 percent. We have also
done studies looking at comparing computerized pharmacokinetic dosing with that of
dosing done empirically by physicians.

Our most recent research activity was in the area of pharmocogenetics. Drug metabolism
is influenced by many factors. It has been known for some time that genetic alterations
of drug metabolizing enzymes can have significant effects on drug disposition. Recent
attention has been focused on genetic polymorphisms and the hepatic cytochrome P-450
enzyme system. Mutations in some of these cytochrome P-450 enzymes can lead to altered
metabolism of drugs resulting in toxic concentrations of the drug, or in some situations
where metabolism is accelerated, to very low levels of a particular drug. Distribution
of these genetic polymorphisms vary depending on ethnic and racial characteristics.
For example, the CYP2D6 enzyme has genetic mutations that result in poor metabolizers
in 5 to 10 percent of Whites, while Asians have a rate of less than 1 percent. In
contrast, studies have shown that up to 29 percent of Blacks are ultra rapid metabolizers.
We have performed studies in Mexican-Americans to determine the incidence of genetic
polymorphisms in the CYP2D6 enzyme system in this population. We found the rate of
the poor metabolizer phenotype and genotype to be similar to non-Mexican-American
Whites with a rate of about 6 percent.

Current research projects are examining the possible benefit of sulfonylureas in combination
with meglitinides in improving glucose control in type 2 diabetics, a study analyzing
the effects of sub-therapeutic INRs on patients treated with warfarin for mechanical
heart valves and a study that analyzes patient compliance and preference for different
warfarin dosing regimens.

In addition to the above investigations, we have been involved in numerous clinical
trials of investigational drugs. The most recent of which was the newly approved Glp-analog,
Exenatide for the treatment of type 2 diabetes.